Teeth are mainly composed of enamel, dentin, and pulp chamber rich with nerves and blood vessels. Enamel and dentin are highly calcified hard tissue because they contain hydroxyapatite (HAp).
In the oral environment, the phosphates and calcium ions in the liquid phase (saliva) and the solid phase (enamel) maintain a dynamic equilibrium between demineralization and remineralization. Demineralization is the process of mineral loss from teeth caused by plaque acids or dietary acids. Demineralization can occur on tooth surfaces or below tooth surfaces depending upon the composition of the acids, concentration and pH. Demineralization may increase due to various factors affecting the balance of the equilibrium. However, inhibition of oral bacterial growth, or buffering of acidity caused by soft drinks or bacteria metabolism may aid tooth repair and prevent/alleviate caries, thereby avoiding pain and tooth loss.
Dental caries is a state of a dental carious cavity caused by the dissolution of hydroxyapatite from teeth (demineralization) which cannot naturally return to a healthy state by saliva remineralization alone. Dental decay and caries usually occur as the result of attack by acids in the mouth or saliva. A lesion or cavity in the enamel thus occurs and, if deep enough, renders the tooth vulnerable to attack by decay-producing bacteria. These acids are readily produced by fermentative catabolism of dietary carbohydrates by various plaque-forming organisms such as S. mutans. Many studies have shown that the consumption of fermentable sugars can result in plaque pH changes below the critical level (pH 5.5) at which enamel starts to dissolve.
Remineralization refers to the process of repair of acid damaged tooth structure by the recrystallization of mineral salts on the tooth architecture. Remineralization processes are a natural protective feature of saliva against the formation of tooth cavities, as saliva is supersaturated with respect to calcium phosphate tooth mineral salts. Remineralization and resistance to demineralization represent primary mechanisms toward the reduction of tooth decay or other acid insults.
In view of the dynamic equilibrium mechanism, remineralization can be improved by increasing the concentration of phosphate ions and calcium ions in the oral environment. Among various calcium phosphate salts, amorphous calcium phosphate (ACP; Ksp: 10−24.8) is a good source of calcium ions and phosphate ions because of its advantageous solubility. However, after ACP contacts with water in a physiological environment, the solubility of ACP decreases as it transforms into crystalline hydroxyapatite (Ca10(PO4)6(OH)2; Ksp: 10−116.8) through phase transformation. Furthermore, ACP only remains in mouth or dental surface for a short time, so it is difficult to fully demonstrate its effect. In 2004, Eric Reynolds of the University of Melbourne, Australia, used peptide fragments produced from enzyme-cleaved casein as carriers to chelate with ACP to form casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and constitute a core-shell structure to stabilize the amorphous structure of ACP and prevent ACP from transforming into crystalline calcium phosphate. This maintains the high solubility of ACP, attaches ACP to oral surfaces securely, keeps ACP for a long term efficacy in preventing caries. Although CPP-ACP is effective in preventing caries, its popularity is limited due to a potential milk protein allergy in some subjects which is triggered by casein.
Taiwan Patent Publication No. 200637587 (U.S. patent application Ser. No. 11/020,010) discloses an oral care composition comprising xylitol. Although the composition can reduce oral acidity and prevent dental caries, the composition fails to prove remineralization effect.
Taiwan Patent Publication No. 200637605 (U.S. patent application Ser. No. 11/256,861) discloses a toothpaste composition comprising a wetting agent, an abrasive, and an antibacterial component including ursolic acid and carnosic acid. The application relates to an anti-bacteria formulation that is irrelevant to remineralization.
Taiwan Patent Publication No. 200640531 (U.S. patent application Ser. No. 11/256,788) discloses an oral care composition comprising oregano for inhibiting bacteria and preventing dental plaque, inflammation and oxidation. However, the composition fails to provide a remineralization effect.
U.S. Pat. Nos. 5,037,639, 5,268,167, 5,437,857, 5,427,768 and 5,460,803 involve various amorphous calcium phosphate compounds (such as amorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride (ACPF) and amorphous calcium carbonate phosphate (ACCP)) for remineralization. However, these compounds are intended for crystallization after contact with water, so they are not suitable for commercialization.
U.S. Pat. No. 5,858,333 provides a two-part oral product capable of remineralizing subsurface lesions and/or mineralizing exposed dentinal tubules in teeth which is composed of cationic and anionic discrete parts. The cationic discrete part contains ACP. However, the ACP in the product cannot stay in continuous contact with teeth for a long time, so its remineralization effect is not satisfactory.
U.S. Patent Application No. 20080171001 provides new toothpaste comprising casein phosphopeptide amorphous calcium phosphate and its remineralization effect is also not satisfactory. Taiwan Patent Application No. 200637587 uses calcium glycerophosphate for teeth remineralization. However, the calcium bonds to glycerophosphate in the calcium glycerophosphate but not glycerol and phosphate separately, and the solubility of the calcium glycerophosphate is relatively low.
Therefore, there is still a need to develop a material with advantageous remineralization effect.